It's a fool who plays it cool by making his world a little colder.mostly silly, with a 20% chance of science

Friday, June 8, 2007

On the Origin of Tumours by Means of Natural Selection

I had an interesting conversation with a medical doctor this week. Granted, I’d much rather he’d chosen not to discuss cancer stem cells while removing a suspicious mole from my arm, but these things often seem to happen to me when a physician asks what I do for a living.

Our conversation got me thinking about how the development of cancer mirrors the process of evolution. This comparison first occurred to me during my undergraduate degree in genetics. To understand the molecular nature of cancer, we had to learn to see things from a tumour cell’s point of view.

Cell growth and division are usually very tightly regulated processes; various mechanisms have evolved to ensure that a cell can only divide into two daughter cells if the conditions are right. The correct growth factor chemicals must be present, DNA replication must have been successfully completed, the cell must have reached a certain minimum size, and be in an appropriate position with respect to other cells and tissues.

A tumour develops when these inhibitory mechanisms fail. DNA replication is not 100% accurate, and some daughter cells will receive mutations in genes that usually help to regulate cell division. Most mutant cells will be weeded out and marked for destruction when they fail to meet other cell division criteria, but the occasional gene mutation escapes notice and survives.

Imagine a mutant cell that no longer requires growth factors in order to grow and divide. The cell will divide regardless of its chemical environment, passing on its mutation to both daughter cells, each of which will then divide into two more mutated cells. In this way the mutation is passed down through successive generations of cells. If there are no growth factors present, the mutant cells will continue to divide while normal cells are inhibited. The mutant cells will rapidly come to outnumber the normal cell population. You might say that they have a selective advantage, and therefore produce more offspring.

Eventually, one of the rapidly dividing, growth-factor independent cells will acquire a second mutation in another inhibitory gene. Suddenly, we have a growth-factor independent cell that will divide when it reaches a smaller size than normal. This cell will be able to divide before its merely growth-factor independent relatives are ready. Again, this mutation confers a selective advantage, and subsequent daughter cells will outcompete and outnumber the original population of mutant cells. As cells grow and divide faster and faster, more DNA copying errors creep in. Some of these errors even increase the frequency of further mutations. The end result of this evolutionary process is a clonal population of aggressively growing cells that can move to other locations in the body to produce secondary tumours.

This process is obviously disastrous for the host. But you can not deny that the tumour cells themselves are immensely successful. Their ability to divide more rapidly than the body’s normal cells lets them produce more offspring, and increase the frequency of their beneficial mutations within the total cell population.

The gradual evolution from normal to malignant cells illustrates a very simple natural law. If an individual produces a number of offspring via an imperfect copying mechanism, the result will be a mixed population of individuals with slightly different characteristics. If one of the variants is able to produce offspring faster than its peers, then those offspring will be over-represented in subsequent generations. In this way, characteristics that increase reproductive success are inherited by more individuals and continue to increase in frequency, gradually changing the overall demographics of the population.

This really should be self-evident, and I have a very hard time understanding why evolution deniers find the concept so difficult to grasp. The gradual accumulation of mutations during cancer development is well documented, but I don’t think I’ve ever seen these data used to teach the principles of evolutionary theory. I fear that I would not make a very good teacher myself as I would become too easily frustrated with those who just can’t seem to get it. But if anyone reading this is involved in science education, please let me know what you think.

Oh, the suspicious mole turned out to be only slightly dodgy. No matter how cool evolution is, I’m happy to avoid observing the survival of the fittest within my own puny Celtic skin.

I confess that I haven't. When I was working in the lab I preferred to read completely unrelated books in my spare time. I still prefer fiction to everything else, but I'm also trying to play catch-up on all the other stuff I should have already read, or have read before and forgotten!

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